Cheng Guanghui, Dai Mingkai, Xin Qian, Wang Lina, Kong Feng, Xu Dawei
Central Research Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University Jinan 250033, PR China.
Engineering Laboratory of Urinary Organ and Functional Reconstruction of Shandong Province 250013, PR China.
Int J Clin Exp Pathol. 2020 Aug 1;13(8):2123-2129. eCollection 2020.
Benign prostatic hyperplasia (BPH) is an age-related disease, occurring in >70% of men of age >60. Because telomeres and telomerase play a key role in aging and age-related diseases, and certain telomerase gene single nucleotide polymorphisms (SNPs) are shown to be associated with the susceptibility to age-related diseases, we wanted to determine the relationship between BPH and leukocyte telomere length (LTL) and telomere length-related single nucleotide polymorphisms (SNPs) of the telomerase holoenzyme genes.
Peripheral blood was collected from both BPH patients and age-matched healthy male controls and genomic DNA was extracted. rs2736100 and rs2736098 at the and rs12696304 at the locus were analysed using pre-designed TaqMan SNP genotyping assay kits. LTL was determined using qPCR.
Patients with BPH had significantly shorter LTL (1.231 ± 0.532 vs 0.899 ± 0.322, P < 0.001). The genotyping results show similar frequencies in rs2736100, rs2736098 and rs12696304 between healthy and BPH individuals.
Shorter telomeres but not telomerase SNPs at the TERT and TERC loci, are associated with BPH. Short telomeres may promote senescence of a fraction of prostatic epithelial cells, while senescent cells in turn facilitate epithelial and stromal cell proliferation by the senescence-associated secretory phenotype mechanism, thereby eventually leading to BPH development.
良性前列腺增生(BPH)是一种与年龄相关的疾病,60岁以上男性中超过70%会发病。由于端粒和端粒酶在衰老及与年龄相关的疾病中起关键作用,且某些端粒酶基因单核苷酸多态性(SNP)显示与对年龄相关疾病的易感性有关,我们想确定BPH与白细胞端粒长度(LTL)以及端粒酶全酶基因的端粒长度相关单核苷酸多态性(SNP)之间的关系。
收集BPH患者和年龄匹配的健康男性对照的外周血并提取基因组DNA。使用预先设计的TaqMan SNP基因分型检测试剂盒分析位于 处的rs2736100和rs2736098以及位于 位点的rs12696304。使用qPCR测定LTL。
BPH患者的LTL显著更短(1.231±0.532对0.899±0.322,P<0.001)。基因分型结果显示,健康个体和BPH个体在rs2736100、rs2736098和rs12696304中的频率相似。
端粒缩短而非TERT和TERC位点的端粒酶SNP与BPH相关。短端粒可能促进一部分前列腺上皮细胞衰老,而衰老细胞反过来通过衰老相关分泌表型机制促进上皮和基质细胞增殖,从而最终导致BPH的发生。